Nolting, JensReuter, SabineStuelten, ChristinaLi, PengSucov, HenryKim, Byung-GyuLetterio, John J.Kretschmer, KarstenDaniel, CarolinKim, Hye-Jungvon Boehmer, Harald2011-11-012009Nolting, Jens, Carolin Daniel, Sabine Reuter, Christina Stuelten, Peng Li, Henry Sucov, Byung-Gyu Kim, et al. 2009. Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines. The Journal of Experimental Medicine 206(10): 2131-2139.0022-1007http://nrs.harvard.edu/urn-3:HUL.InstRepos:5336035It has been reported that retinoic acid (RA) enhances regulatory T (T reg) cell conversion by inhibiting the secretion of cytokines that interfere with conversion. This report shows that these conclusions provide a partial explanation at best. First, RA not only interfered with cytokine secretion but also with the ability of these cytokines to inhibit T reg cell conversion of naive T cells. Furthermore, RA enhanced conversion even in the absence of inhibitory cytokines. The latter effect depended on the RA receptor α (RARα) but did not require Smad3, despite the fact that RA enhanced Smad3 expression. The RARα1 isoform was not essential for RA-dependent enhancement of transforming growth factor β–driven conversion, suggesting that conversion can also be mediated by RARα2. Interleukin (IL)-6 strongly reduced RARα expression levels such that a deficiency of the predominant RARα1 isoform leaves too little RARα2 for RA to inhibit the generation of Th17 cells in the presence of IL-6.en-USJournal Article2011-11-0110.1084/jem.20090639